Sarcolemmal reorganization in facioscapulohumeral muscular dystrophy
Article first published online: 25 JAN 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 59, Issue 2, pages 289–297, February 2006
How to Cite
Reed, P., Porter, N. C., Strong, J., Pumplin, D. W., Corse, A. M., Luther, P. W., Flanigan, K. M. and Bloch, R. J. (2006), Sarcolemmal reorganization in facioscapulohumeral muscular dystrophy. Ann Neurol., 59: 289–297. doi: 10.1002/ana.20750
- Issue published online: 25 JAN 2006
- Article first published online: 25 JAN 2006
- Manuscript Accepted: 21 OCT 2005
- Manuscript Revised: 20 OCT 2005
- Manuscript Received: 6 JUL 2005
- Bronfman and Delta Railroad Fellowships from the FSH Society
- Muscular Dystrophy Association
- NIH (National Institutes of Neurological Diseases and Stroke.). Grant Number: R21 NS43976
- NIH (National Center for Research Resources) to the University of Utah. Grant Number: M01-RR00064
We examined the sarcolemma of skeletal muscle from patients with facioscapulohumeral muscular dystrophy (FSHD1A) to learn if, as in other murine and human muscular dystrophies, its organization and relationship to nearby contractile structures are altered.
Unfixed biopsies of control and FSHD deltoid and biceps muscles, snap-frozen at resting length, were cryosectioned, indirectly immunolabeled with fluorescent antibodies to sarcolemmal and myofibrillar markers, and examined with confocal microscopy to localize the immunolabeled proteins. Glutaraldehyde-fixed samples were stained with heavy metals, embedded, thin-sectioned, and examined with electron microscopy to determine the relationship between the sarcolemma and the underlying myofibrils.
Confocal microscopy showed that some of the structures at the sarcolemma in FSHD samples were misaligned with respect to the underlying contractile apparatus. Electron microscopy showed a significant increase in the distance between the sarcolemma and the nearest myofibrils, from less than 100nm in controls to values as high as 550nm in FSHD.
Our results show that the pathophysiology of FSHD includes novel changes in the organization of the sarcolemma and its association with nearby contractile structures and suggest that, as in other muscular dystrophies, the integrity of the sarcolemma may be compromised in FSHD. Ann Neurol 2006;59:289–297